Mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)

Mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) is a serine/threonine-protein kinase and an upstream component of the MAPK signal transduction cascade[1][3][5]. It is involved in the activation of the stress-activated protein kinase/JNK pathway and, to a lesser extent, the p38 MAPK pathway, and is necessary for efficient activation by stimuli such as LPS, TNF-alpha, and various pathogen-associated molecular patterns[1][3][5]. MAP4K2 also acts as a direct kinase for LATS1/2, linking it to regulation of the Hippo pathway and the effectors YAP and TAZ, which are pivotal in organ size control, cell proliferation, and tumor suppression[3]. Additional interactions include roles in vesicle trafficking and B-cell differentiation, particularly in lymphoid follicles[3]. Multiple aliases and gene/protein identifiers are in use (GCK, RAB8IP), and the protein is expressed in a range of tissues, with immune system significance highlighted by its action in response to immune stimuli[1][3][6]. There are currently no approved drugs targeting MAP4K2 in clinical practice[2][4].

Other names

GCKRAB8IPBL44Germinal center kinase

For research compounds, presumed inhibition or modulation of kinase activity (MAP4K2 inhibition would reduce JNK/p38 MAPK pathway activation or Hippo pathway regulation)